Giuseppe
Emeritus
High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses (PNAS, abstract, edited)
[Source: Proc Natl Acad Sci USA, full text: <cite cite="http://www.pnas.org/content/early/2011/02/23/1019109108.abstract">High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses ? PNAS</cite>. Abstract, edited.]
High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses
1. Yipeng Sun a,1, 2. Kun Qin b,1, 3. Jingjing Wang a, 4. Juan Pu a, 5. Qingdong Tang a, 6. Yanxin Hu a, 7. Yuhai Bi a,c, 8. Xueli Zhao a, 9. Hanchun Yang a, 10. Yuelong Shu b, and 11. Jinhua Liu a,d,2
Author Affiliations
1. a Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
2. b Chinese National Influenza Center, State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China;
3. d The Shandong Animal Disease Control Center, Jinan, Shandong 250022, China; and
4. c CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved January 28, 2011 (received for review December 21, 2010)
* ↵1Y. Sun and K.Q. contributed equally to this work.
* 2 To whom correspondence should be addressed. E-mail: ljh@cau.edu.cn.
Abstract
H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort. To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice. These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses. All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk. Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity. Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.
Footnotes
* Author contributions: Y. Sun, J.P., and J.L. designed research; Y. Sun, K.Q., J.W., Q.T., Y.H., Y.B., and X.Z. performed research; K.Q. and J.L. contributed new reagents/analytic tools; Y. Sun, K.Q., J.P., Q.T., Y.H., H.Y., Y. Shu, and J.L. analyzed data; and Y. Sun, K.Q., J.W., and J.L. wrote the paper.
* The authors declare no conflict of interest.
* The sequences reported in this paper have been deposited in the GenBank database [accession nos. GQ373026 (HB08, PB2 gene), GQ373043 (HB08, PB1 gene), GQ373060 (HB08, PA gene), GQ373077 (HB08, HA gene), GQ373094 (HB08, NP gene), GQ373111 (HB08, NA gene), GQ373128 (HB08, M gene), GQ373144 (HB08, NS gene), HQ698624 (BJ09, PB2 gene), HQ698625 (BJ09, PB1 gene), HQ698626 (BJ09, PA gene), HQ698627 (BJ09, HA gene), HQ698628 (BJ09, NP gene), HQ698629 (BJ09, NA gene), HQ698630 (BJ09, M gene), and (BJ09, NS gene)].
* This article is a PNAS Direct Submission.
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1019109108/-/DCSupplemental.
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High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses
1. Yipeng Sun a,1, 2. Kun Qin b,1, 3. Jingjing Wang a, 4. Juan Pu a, 5. Qingdong Tang a, 6. Yanxin Hu a, 7. Yuhai Bi a,c, 8. Xueli Zhao a, 9. Hanchun Yang a, 10. Yuelong Shu b, and 11. Jinhua Liu a,d,2
Author Affiliations
1. a Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
2. b Chinese National Influenza Center, State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China;
3. d The Shandong Animal Disease Control Center, Jinan, Shandong 250022, China; and
4. c CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved January 28, 2011 (received for review December 21, 2010)
* ↵1Y. Sun and K.Q. contributed equally to this work.
* 2 To whom correspondence should be addressed. E-mail: ljh@cau.edu.cn.
Abstract
H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort. To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice. These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses. All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk. Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity. Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.
Footnotes
* Author contributions: Y. Sun, J.P., and J.L. designed research; Y. Sun, K.Q., J.W., Q.T., Y.H., Y.B., and X.Z. performed research; K.Q. and J.L. contributed new reagents/analytic tools; Y. Sun, K.Q., J.P., Q.T., Y.H., H.Y., Y. Shu, and J.L. analyzed data; and Y. Sun, K.Q., J.W., and J.L. wrote the paper.
* The authors declare no conflict of interest.
* The sequences reported in this paper have been deposited in the GenBank database [accession nos. GQ373026 (HB08, PB2 gene), GQ373043 (HB08, PB1 gene), GQ373060 (HB08, PA gene), GQ373077 (HB08, HA gene), GQ373094 (HB08, NP gene), GQ373111 (HB08, NA gene), GQ373128 (HB08, M gene), GQ373144 (HB08, NS gene), HQ698624 (BJ09, PB2 gene), HQ698625 (BJ09, PB1 gene), HQ698626 (BJ09, PA gene), HQ698627 (BJ09, HA gene), HQ698628 (BJ09, NP gene), HQ698629 (BJ09, NA gene), HQ698630 (BJ09, M gene), and (BJ09, NS gene)].
* This article is a PNAS Direct Submission.
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1019109108/-/DCSupplemental.
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